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E7 proteins from high- and low-risk human papillomaviruses bind to TGF-β-regulated Smad proteins and inhibit their transcriptional activity

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Summary.

Human papillomaviruses (HPV) infect keratinocytes of skin and mucosa. Persistent infection can lead to the formation of benign tumors. In cases of high-risk HPV, such as HPV16 or 18, these may further progress to cancer. In order to support viral replication in suprabasal keratinocytes, the HPV E7 protein employs various strategies to keep keratinocytes in cycle and counteracts anti-proliferative signals from outside. HPV16 E7 can directly interfere with transforming growth factor-β (TGF-β) signalling by binding to Smad proteins mediating growth arrest. It has been speculated that this property of HPV16 E7 contributes to HPV-associated carcinogenesis. Here, we show that E7 proteins from different low- and high-risk HPV types bind to Smad 1 to 4. The E7 protein from HPV1, a low-risk HPV causing plantar warts, efficiently inhibited Smad 3-induced transcription. Our data strongly indicate that the Smad-binding capacity of E7 proteins from different HPVs may preserve keratinocyte proliferation required for the productive viral life cycle rather than promoting carcinogenesis.

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Authors and Affiliations

  1. Institute of Virology, University of Cologne, Cologne, Germany

    M. Habig, V. S. Dole, H. Pfister & S. Smola-Hess

  2. Department of Dermatology, University of Cologne, Cologne, Germany

    H. Smola

  3. Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA, USA

    R. Derynck

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  1. M. Habig
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  2. H. Smola
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Habig, M., Smola, H., Dole, V. et al. E7 proteins from high- and low-risk human papillomaviruses bind to TGF-β-regulated Smad proteins and inhibit their transcriptional activity. Arch Virol 151, 1961–1972 (2006). https://doi.org/10.1007/s00705-006-0768-1

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